The project is designed to provide information about the organization of neuronal systems in the mammalian spinal cord that are involved in motor control, as studied in adult cats in vivo and in the isolated brain stem and spinal cord of neonatal rats or mice studied in vitro. Current interest centers on the organization of excitatory last-order interneurons in reflex pathways within the spinal segment, control of information flow in them exerted by other inputs from primary afferent and supraspinal descending systems, and their interaction with the spinal mechanisms that generate rhythmic motoneuron output patterns underlying locomotion. In the cat, we are particularly concerned with interneurons that transmit short-latency excitation from low-threshold skin afferents and from reticulospinal and vestibulospinal systems. All of these systems produce minimally disynaptic excitation in some species of lumbosacral motoneurons and all are powerfully modulated by the spinal central pattern generator (CPG) for locomotion during fictive stepping in decerebrate animals. Differential patterns of CPG modulation are being used to identify separate systems of segmental interneurons, each with highly specific patterns of primary afferent and descending convergence, that are present in the mammalian spinal cord. Work on the in vitro preparation of neonatal rodent spinal cord, with or without the brain stem, is designed in part to develop preparations that can be used to investigate functionally defined reflex pathways, in order to compliment work in the cat. This requires functional isolation of identified peripheral nerves and intracellular recording from select populations of motoneurons and interneurons. We are also investigating a neurological mutant mouse, oscillator (OSC), which has a defect in the alpha-1 subunit of the glycine receptor. Attempts are being made to quantitate glycine receptor function at various postnatal ages, using recurrent inhibition. Unfortunately, glycinergic recurrent inhibition in the in vitro preparation is usually superimposed on a glutamatergic synaptic excitation of unknown origin, making it difficult to study glycine responses in isolation. Pharmacological dissection of the responses is being used to deal with this problem.